Transversely isotropic elasticity imaging of cancellous bone

To measure spatial variations in mechanical properties of biological materials, prior studies have typically performed mechanical tests on excised specimens of tissue. Less invasive measurements, however, are preferable in many applications, such as patient-specific modeling, disease diagnosis, and tracking of age- or damage-related degradation of mechanical properties. Elasticity imaging (elastography) is a nondestructive imaging method in which the distribution of elastic properties throughout a specimen can be reconstructed from measured strain or displacement fields. To date, most work in elasticity imaging has concerned incompressible, isotropic materials. This study presents an extension of elasticity imaging to three-dimensional, compressible, transversely isotropic materials. The formulation and solution of an inverse problem for an anisotropic tissue subjected to a combination of quasi-static loads is described, and an optimization and regularization strategy that indirectly obtains the solution to the inverse problem is presented. Several applications of transversely isotropic elasticity imaging to cancellous bone from the human vertebra are then considered. The feasibility of using isotropic elasticity imaging to obtain meaningful reconstructions of the distribution of material properties for vertebral cancellous bone from experiment is established. However, using simulation, it is shown that an isotropic reconstruction is not appropriate for anisotropic materials. It is further shown that the transversely isotropic method identifies a solution that predicts the measured displacements, reveals regions of low stiffness, and recovers all five elastic parameters with approximately 10% error. The recovery of a given elastic parameter is found to require the presence of its corresponding strain (e.g., a deformation that generates ??? is necessary to reconstruct C????), and the application of regularization is shown to improve accuracy. Finally, the effects of noise on reconstruction quality is demonstrated and a signal-to-noise ratio (SNR) of 40 dB is identified as a reasonable threshold for obtaining accurate reconstructions from experimental data. This study demonstrates that given an appropriate set of displacement fields, level of regularization, and signal strength, the transversely isotropic method can recover the relative magnitudes of all five elastic parameters without an independent measurement of stress. The quality of the reconstructions improves with increasing contrast, magnitude of deformation, and asymmetry in the distributions of material properties, indicating that elasticity imaging of cancellous bone could be a useful tool in laboratory studies to monitor the progression of damage and disease in this tissue.     

A theoretical model to predict distribution of the fabric tensor and apparent density in cancellous bone

 The adaptation of cancellous bone to mechanical forces is well recognized. Theoretical models for predicting cancellous bone architecture have been developed and have mainly focused on the distribution of trabecular mass or the apparent density. The purpose of this study was to develop a theoretical model which can simultaneously predict the distribution of trabecular orthotropy/orientation, as represented by the fabric tensor, along with apparent density. Two sets of equations were derived under the assumption that cancellous bone is a biological self-optimizing material which tends to minimize strain energy. The first set of equations provide the relationship between the fabric tensor and stress tensor, and have been verified to be consistent with Wolff’s law of trabecular architecture, that is, the principal directions of the fabric tensor coincide with the principal stress trajectories. The second set of equations yield the apparent density from the stress tensor, which was shown to be identical to those obtained based on local optimization with strain energy density of true bone tissue as the objective function. These two sets of equations, together with elasticity field equations, provide a complete mathematical formulation for the adaptation of cancellous bone. Received: 25 February 1997/Revised version: 23 September 1997     

Glenoid cancellous bone strength and modulus.

The objectives of this study were to determine the strength and modulus of glenoid cancellous bone, including regional variations. The motivations were: to select a suitable bone substitute for standardized testing of glenoid prosthesis loosening, to assist in shoulder prosthesis design and to provide input data for finite element analyses. Ten glenoids from eight cadavers (mean age, 81) were tested by in situ indentation. Mean strength ranged from 6.7 to 17 MPa for the ten glenoids, the overall mean being 10.3 MPa. Mean E moduli ranged from 67 to 171 MPa for the individual glenoids, the overall mean being 99 MPa. These values are likely at the lower end of what would be expected for normal bone since strength and modulus decrease with age and the available specimens were older. These values may be appropriate for prosthesis design, however, since mechanical properties are reduced in rheumatoid arthritic bone. Regional trends were very similar for modulus and strength. The strongest region was postero-superior. The central column, correlating with the keel position in many glenoid components, was weaker than both the anterior and posterior regions but deeper. A large drop in strength and modulus below the subchondral layer emphasizes the importance of maintaining this layer during prosthetic replacement.     

The contribution of cancellous bone to long bone strength and rigidity

A recent article (Burr and Piotrowski, 1982) suggested that structural analyses of long bone cross-sectional geometry will be inaccurate and should be considered inappropriate when cancellous bone accounts for 10-15% or more of the cross-sectional area. Consideration of material property differences between compact and cancellous bone, however, indicates that even significant proportions of cancellous bone (10-40% of total cross-sectional area) will very likely have negligible effects on bone strength and rigidity, and can be effectively ignored in geometrical analyses of diaphyseal sections. In metaphyseal and epiphyseal regions, however, geometric analyses of section properties such as area moments of inertia are inappropriate, both because of significant trabecular bone effects, and because of the inherent constraints of mechanical beam models.     

Influence of boundary conditions on computed apparent elastic properties of cancellous bone

High-resolution finite element models of trabecular bone can be used to study trabecular structure–function relationships, elasticity, multiaxial strength, and tissue remodelling in more detail than experiments. Beside effects of the model size, scan/analysis resolution, segmentation process, etc., the type of the applied boundary conditions (BCs) have a strong influence on the predicted elastic properties. Appropriate BCs have to be applied on hexahedral digital finite element models in order to obtain effective elastic properties. Homogeneous displacement BCs as proposed by Van Rietbergen et al. (J Biomech 29(12):1653–1657, 1996) lead to “apparent” rather than to “effective” elastic properties. This study provides some answers concerning such differences by comparing various BC types (uniform displacement, mixed BCs, periodic BCs), different volume element definitions (original and mirrored models), and several bone volume fractions (BVTV ranging from 6.5 to 37.6%). First, the mixed BCs formulated by Hazanov (Arch Appl Mech 68(6):385–394, 1998) are theoretically extended to shear loading of a porous media. Second, six human bone samples are analyzed, their orthotropic Young’s moduli, shear moduli, and Poisson’s ratios computed and compared. It is found that the proposed mixed BCs give exactly the same effective elastic properties as periodic BCs if a periodic and orthotropic micro-structured material is used and thus denoted as “periodicity compatible” mixed uniform BCs (PMUBCs). As bone samples were shown to be nearly orthotropic for volume element side lengths ≥5 mm the proposed mixed BCs turn out to be the best choice because they give again essentially the same overall elastic properties as periodic BCs. For bone samples of smaller dimensions ( < 5 mm) with a strong anisotropy (beyond orthotropy) uniform displacement BCs remain applicable but they can significantly overestimate the effective stiffness. In Memoriam, Prof. Christian Huet.     

The fabric dependence of the orthotropic elastic constants of cancellous bone

It has been proposed that the orthotropic elastic constants of cancellous bone depend upon a tensorial measure of anisotropy called fabric as well as the tissue's structural density. Cowin (1985, Mechanics Mater, 4, 137-147; 1986, J. biomech. Engng 108, 83-88) developed explicit relationships for the elastic constant, structural density and fabric relationship. In this study the orthotropic elastic moduli, structural density, and fabric components were measured for 11 cancellous bone specimens from five bovine femora and for 75 specimens from three human proximal tibiae and fitted to these relationships using a least squares analysis. The relationships explained between 72 and 94% of the variance in the elastic constants. The relationships between the elastic constants and squared or cubed power functions of structural density had better predictive value over the entire distribution of the data than did expressions with linear functions of structural density.     

Finite element calculated uniaxial apparent stiffness is a consistent predictor of uniaxial apparent strength in human vertebral cancellous bone tested with different boundary conditions

Strong correspondence between the uniaxial apparent strength and stiffness of cancellous bone allows the use of stiffness as a predictor of bone strength. Measured values of mechanical properties in cancellous bone can be different between experiments due to different experimental conditions. In the current study, bone volume fraction, experimentally determined and finite element (FE) predicted stiffness were examined as predictors of cancellous bone ultimate strength in two different groups each of which was tested using a different end constraint. It is demonstrated that, although always significant, the relationships of strength with bone volume fraction and experimentally determined stiffness are different between test groups. Apparent stiffness, estimated by FE modeling, predicts the ultimate strength of human cancellous bone consistently for all examined experimental protocols.     

The dependence of the elastic properties of osteoporotic cancellous bone on volume fraction and fabric

Osteoporosis is a progressive systemic skeletal condition characterized by low bone mass and microarchitectural deterioration, with a consequent increase in susceptibility to fracture. Hence, osteoporosis would be best diagnosed by in vivo measurements of bone strength. As this is not clinically feasible, our goal is to estimate bone strength through the assessment of elastic properties, which are highly correlated to strength. Previously established relations between morphological parameters (volume fraction and fabric) and elastic constants could be applied to estimate cancellous bone stiffness in vivo. However, these relations were determined for normal cancellous bone. Cancellous bone from osteoporotic patients may require different relations. In this study we set out to answer two questions. First, can the elastic properties of osteoporotic cancellous bone be estimated from morphological parameters? Second, do the relations between morphological parameters and elastic constants, determined for normal bone, apply to osteoporotic bone as well? To answer these questions we used cancellous bone cubes from femoral heads of patients with (n=26) and without (n=32) hip fractures. The elastic properties of the cubes were determined using micro-finite element analysis, assuming equal tissue moduli for all specimens. The morphological parameters were determined using microcomputed tomography. Our results showed that, for equal tissue properties, the elastic properties of cancellous bone from fracture patients could indeed be estimated from morphological parameters. The morphology-based relations used to estimate the elastic properties of cancellous bone are not different for women with or without fractures.     

Some basic relationships between density values in cancellous and cortical bone

Density is a salient property of bone and plays a crucial role in determining the mechanical properties of both its cancellous and cortical structural forms. Density is defined in a number of ways at either the bone tissue (D(app), apparent) or the bone material level (D(mat), material). The concept of density is relatively simple, but measuring it in the context of bone is a complex issue. The third dimension of the problem is the concept of porosity, or BV/TV (ratio of bone material volume over tissue volume). Recent investigations from our laboratory have revealed an interdependence of D(app) and D(mat) in the cancellous bone of at least four different cohorts of human patients. To clarify the underlying causes of this behaviour, we produced here equivalent relationships from specimens originating from cortical and cancellous areas of the same bone. Plots of D(app) vs. D(mat) showed that D(mat) was not a monotonic function of increasing D(app), but instead showed a 'boomerang'-like pattern. By empirically dissecting the data in two regions for D(app) above and below a value equal to 1.3gcm(-3), we were able to objectively isolate the bone in trabecular and compact forms. Our findings may have implications not only for the segregation of bone in these two structural forms, but also for the mechanobiological and physiological processes that govern the regulation of compact and trabecular bone areas.     

On the meaning of density dependence

Summary Despite a long history, the term density dependence lacks a generally accepted definition. A definition is offered that seems consistent with most other definitions and general usage, that is, a density-dependent factor is any component of the environment whose intensity is correlated with population density and whose action affects survival and reproduction. This definition is used in evaluating the role of territorial behavior, the availability of nest sites, and competition in determining the size of a population. Because neither territory size nor the number of nest sites is correlated with either density or with changes in the birth and death rates of these populations, these cannot be considered density-dependent factors. Competition determines who does breed and who does not rather than the number of breeders, and thus it is not a density-dependent factor determining a population's size.     

Tensile properties of rat femoral bone as functions of bone volume fraction, apparent density and volumetric bone mineral density

Mechanical testing has been regarded as the gold standard to investigate the effects of pathologies on the structure-function properties of the skeleton. Tensile properties of cancellous and cortical bone have been reported previously; however, no relationships describing these properties for rat bone as a function of volumetric bone mineral density (ρ(MIN)), apparent density or bone volume fraction (BV/TV) have been reported in the literature. We have shown that at macro level, compression and torsion properties of rat cortical and cancellous bone can be well described as a function of BV/TV, apparent density or ρ(MIN) using non-destructive micro-computed tomographic imaging and mechanical testing to failure. Therefore, the aim of this study is to derive a relationship expressing the tensile properties of rat cortical bone as a function of BV/TV, apparent density or ρ(MIN) over a range of normal and pathologic bones. We used bones from normal, ovariectomized and osteomalacic animals. All specimens underwent micro-computed tomographic imaging to assess bone morphometric and densitometric indices and uniaxial tension to failure. We obtained univariate relationships describing 74-77% of the tensile properties of rat cortical bone as a function of BV/TV, apparent density or ρ(MIN) over a range of density and common skeletal pathologies. The relationships reported in this study can be used in the structural rigidity to provide a non-invasive method to assess the tensile behavior of bones affected by pathology and/or treatment options.     

The effect of charge density on the velocity and attenuation of ultrasound waves in human cancellous bone

Cancellous bone is a highly porous material, and two types of waves, fast and slow, are observed when ultrasound is used for detecting bone diseases. There are several possible stimuli for bone remodelling processes, including bone fluid flow, streaming potential, and piezoelectricity. Poroelasticity has been widely used for elucidating the bone fluid flow phenomenon, but the combination of poroelasticity with charge density has not been introduced. Theoretically, general poroelasticity with a varying charge density is employed for determining the relationship between wave velocity and attenuation with charge density. Fast wave velocity and attenuation are affected by porosity as well as charge density; however, for a slow wave, both slow wave velocity and attenuation are not as sensitive to the effect of charge density as they are for a fast wave. Thus, employing human femoral data, we conclude that charged ions gather on trabecular struts, and the fast wave, which moves along the trabecular struts, is significantly affected by charge density.     

Anisotropy and inhomogeneity of the trabecular structure can describe the mechanical strength of osteoarthritic cancellous bone

Osteoarthritic cancellous bone was studied to investigate the development of this pathology, and the functional changes it induces in the bone. In order to predict how the morphological alterations of the tissue induced by the pathology can change the mechanical properties of the structure, two different strategies have been used in the literature: (1) emphasising the influence of structural anisotropy; (2) stressing the highly inhomogeneous characteristics of cancellous bone. The aim of the present study was to verify the theory that mechanical strength of osteoarthritic cancellous bone depends both on tissue anisotropy and inhomogeneity.Twenty-five specimens were extracted from osteoarthritic femoral heads, along selected directions, and analysed by means of a microtomograph. The same specimens were mechanically tested in compression to determine the mechanical strength. The most representative structural parameters, confirmed by a stepwise analysis, were used to define four models to describe the measured mechanical strength. The models were applied neglecting (global analysis) or considering (local analysis) tissue inhomogeneities to verify whether the correlation with ultimate stress could be improved.The coefficient of determination increased from 0.53, considering only bone volume fraction, up to 0.88, combining it with off-axis angle and normalised eigenvalue. A further improvement was found performing a local analysis (R²=0.90), which corresponded to a decrease of 17% in the residual error.The proposed approach of considering both tissue anisotropy and inhomogeneity improved the accuracy in predicting the mechanical behaviour of cancellous bone tissue and should be suitable for more general loading conditions.     

The dependence of transversely isotropic elasticity of human femoral cortical bone on porosity

The objective of this study was to examine the dependence of the elastic properties of cortical bone as a transversely isotropic material on its porosity. The longitudinal Young's modulus, transverse Young's modulus, longitudinal shear modulus, transverse shear modulus, and longitudinal Poisson's ratio of cortical bone were determined from eighteen groups of longitudinal and transverse specimens using tensile and torsional tests on a servo-hydraulic material testing system. These cylindrical waisted specimens of cortical bone were harvested from the middle diaphysis of three pairs of human femora. The porosity of these specimens was assessed by means of histology. Our study demonstrated that the longitudinal Young's and shear moduli of human femoral cortical bone were significantly (p<0.01) negatively correlated with the porosity of cortical bone. Conversely, the elastic properties in the transverse direction did not have statistically significant correlations with the porosity of cortical bone. As a result, the transverse elastic properties of cortical bone were less sensitive to changes in porosity than those in the longitudinal direction. Additionally, the anisotropic ratios of cortical bone elasticity were found to be significantly (p<0.01) negatively correlated with its porosity, indicating that cortical bone tended to become more isotropic when its porosity increased. These results may help a number of researchers develop more accurate micromechanics models of cortical bone.     

Femoral head apparent density distribution predicted from bone stresses

A new theory relating bone morphology to applied stress is used to predict the apparent density distribution in the femoral head and neck. Cancellous bone is modeled as a self-optimizing material and cortical bone as a saturated (maximum possible bone density) response to stress in the bone tissue. Three different approaches are implemented relating bone apparent density to: (1) the von Mises stress, (2) the strain energy density in the mineralized tissue and (3) a defined closed effective stress (spherical stress). An iterative nonlinear three-dimensional finite element model is used to predict the apparent density distribution in the femoral head and neck for each of the three approaches. It is shown that the von Mises stress (an open effective stress) cannot accurately predict bone apparent density. It is shown that strain energy density and the defined closed effective stress can predict apparent density and that they give predictions consistent with the observed density pattern in the femoral head and neck.     

Does cancellous screw insertion torque depend on bone mineral density and/or microarchitecture?

During insertion of a cancellous bone screw, the torque level reaches a plateau, at the engagement of all the screw threads prior to the screw head contact. This plateau torque (T_Plateau) was found to be a good predictor of the insertion failure torque (stripping) and also exhibited strong positive correlations with areal bone mineral density (aBMD) in ovine bone. However, correlations between T_Plateau and aBMD, as well as correlations between T_Plateau and bone microarchitecture, have never been explored in human bone.     

Intraspecific variation in the strength of density dependence in aphid populations

Abstract.  1. Experimental evidence is presented for positive, negative, and no density dependence from 32 independent density manipulations of milkweed aphids ( Aphis nerii ) in laboratory and field experiments. This substantial variation in intraspecific density dependence is associated with temperature and host-plant species.
2. It is reported that as population growth rate increases, density dependence becomes more strongly negative, suggesting that the monotonic definition of density dependence used in many common population models is appropriate for these aphids, and that population growth rate and carrying capacity are not directly proportional.
3. For populations that conform to these assumptions, population growth rate may be widely applicable as a predictor of the strength of density dependence.